The present invention relates to a pharmaceutical composition that effectively treats neuronal damage, such as damage of peripheral nerves or damage of central nerves, and neurological diseases, such as neuropathy, neuropathic pain or cerebropathy, by repairing damaged nerve tissues.
Various neurological diseases, such as Parkinson's disease, Alzheimer's disease, Huntington's disease, spino cerebellar degeneration, amyotrophic lateral sclerosis, polyneuropathy, spinal cord damage, cerebrovascular disorder, or the like, develop due to degeneration, reduction, cell death, or damage or exclusion of brain or peripheral neurons caused by, for example, environmental or hereditary factors. Accordingly, in treating these neurological diseases, it is important to either compensate for a neuron delivery material that is removed by damage of neurons or regenerate neurons. To regenerate neurons, an undifferentiated neuron stem cell, an embryonic stem cell that can be differentiated into various other cells, etc. may be used.
A great deal of research has been performed on neuron regeneration of damaged neuron. In general, a clinical physical treatment method on traumatic damage of peripheral neurons includes complicated and sequential steps: first, a damaged tissue near a damaged tropical region is removed and then, environments that enable regeneration of peripheral neurons (Kline, J Neurosurg, 1989, 70: 166-174) are provided. Typically, the physical process includes a direct connection or fusion between a portion that is located closer to the damaged region and a farther portion (Kline and Judice, J Neurosurg, 1983, 58: 631-649). During waiting for spontaneous regeneration of neurons, an additional physical method, such as peripheral neuron transplantation (Millesi, Clin Orthop Relat R, 1988, 237: 36-42), is used, as well as a more prudent outpatients treatment, such as maintaining of electrical excitation to generate contraction of muscle to help suppression of deterioration of a muscle-neuron unity (Kim et al., Korean Academy of Rehabilitation Medicine (Korean), 1999, 23: 893-898; al-Amood et al., J Physiol (Lond), 1991, 441: 243-256). Also, these processes still include a comprehensive physical treatment method including a long-term and controlled exercise therapy to prevent weakness and contraction of muscle and to promote neuron blast (Pyun et al., Korean Academy of Rehabilitation Medicine (Korean), 1999, 23: 1063-1075).
Recently, a report was disclosed that neurogenesis in the hippocampus of an adult brain has been reported, and the report has led to development of a method of treating neurological disease by stimulating neuron stem cells in a patient's brain with, for example, a drug to induce regeneration thereof. However, the method requires injection of protein or a protein factor into the brain and is not applicable to general practices. Accordingly, as an alternative to the protein, a low molecular weight compound salvianolic acid B or lithium or a pharmaceutically available salt thereof has been introduced.
Also, damage of peripheral neuron induces a change in a cell body of sensory neuron located at dorsal root ganglion (DRG) for promoting survival and regeneration of axon. For example, after crushing injury, under improved disorder conditions, most neuron fibers are successfully regenerated. However, in many clinical situations, traumatic or disease-induced neuron damage results in limited repair and, in general, substantial delay. In this case, neuropathic or chronic pain may develop.
A representative example of neuropathic pain includes herpes zoster and post-herpetic neuralgia, and these neuropathic pains are, in many cases, comparable to a labor pain which is known as the strongest pain in the life, in terms of a pain level. Also, unlike other diseases causing strong pain, such as terminal cancerous pain, gouty seizure, and trigeminal neuralgia, they are continuous pain, not periodical pain.
Regarding herpes zoster, currently available antivirus agents, for example, acyclovir, valaciclovir, famciclovir, and penciclovir, as described in their prescription guide lines, are therapeutically effective to a certain level only when used within 72 hours after initial rash of herpes zoster. However, many patients visit hospitals after the 72 hours. Accordingly, their effectiveness is reduced in half.
Furthermore, regarding herpes zoster and post-herpetic neuralgia, allopathic agents for reducing neuralgia are used. Examples of the allopathic agents are a non steroidal anti-inflammatory analgesic drug, such as acetaminophen or piroxicam; a narcotic analgesic, such as morphine, oxycodone, pentanyl, or codein; an antiepileptic, such as gabapentin, pregabalin, or valproate; an antidepressant, such as nortriptyline, desipramine, or amitriptyline; an adrenal cortex hormone, such as prednisolone; and a topical anesthetic, such as lidocaine. However, typically, the allopathic agents are not effective and if pain is strong or lasts long, neuron blocking techniques are actively used.
Currently, a prescription for the herpes zoster treatment mainly includes use of an antivirus agent and an anti-inflammatory analgesic drug, and is not effective for repairing damaged nerve tissue, which is an etiological factor of herpes zoster and post-herpetic neuralgia. Thus, it is impossible to effectively control pain.
Also, there is an increasing demand for developing a therapeutic agent for directly preventing or treating a disease that induces damage of nerve tissue, like herpes zoster and post-herpetic neuralgia. Examples of such a disease are neuropathy or neuropathic pain, such as acute inflammatory demyelinating peripheral polyneuropathy, chronic inflammatory demyelinating peripheral polyneuropathy, diabetic peripheral neuropathy, vasculitis neuropathy, hereditary peripheral neuropathy, stroke, brain tumor, degenerative neurological disease, painful diabetic peripheral neuropathy, trigeminal neuralgia, carcinomatous neuro-pathy occurring along cerebral cortex or spinothalamic tract, post-traumatic neuropathy, phantom limb pain, post-stroke central pain, or thalamic pain, and cerebropathy, such as stroke, brain tumor, dementia, Parkinson's disease, Alzheimer's disease, Huntington's disease, epilepsy, dementia, or ischemic cerebropathy.
Accordingly, a drug for effectively treating neuronal damage or neurological disease by rapidly repairing damage of nerve tissue needs to be developed.